Fibronectin is a normal component of the extracellular matrix (ECM). The EDB domain is a splice variant that is highly and specifically expressed during embryonic development and in the neovasculature (newly formed blood vessels) of malignant tumors, but is undetectable in the ECM of healthy adult tissues (except for the endometrium and some placental structures). This makes EDB-fibronectin an excellent tumor angiogenesis marker. By utilizing the high-affinity L19 antibody fragment, bifikafusp alfa selectively homes to tumor blood vessels. Once localized, the fused IL-2 engages IL-2 receptors (primarily the high-affinity heterotrimeric receptor) on nearby immune cells, particularly CD8+ cytotoxic T cells and NK cells. This triggers their local activation, proliferation, and enhancement of cytotoxic function, creating a potent anti-tumor immune response directly within the tumor while sparing healthy tissues from systemic IL-2 exposure.